Clathrin and AP2 are required for phagocytic receptor-mediated apoptotic cell clearance in Caenorhabditis elegans.
Clathrin and AP2 are required for phagocytic receptor-mediated apoptotic cell clearance in Caenorhabditis elegans.
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网格蛋白和 AP2 是秀丽隐杆线虫吞噬细胞受体介导的凋亡细胞清除所必需的
DOI：
10.1371/journal.pgen.1003517
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发表时间：
2013-05
期刊：
影响因子：
4.5
通讯作者：
Yang C
中科院分区：
文献类型：
--
作者：
Chen D;Jian Y;Liu X;Zhang Y;Liang J;Qi X;Du H;Zou W;Chen L;Chai Y;Ou G;Miao L;Wang Y;Yang C
网格蛋白和多亚基接头蛋白复合物AP2在网格蛋白介导的内吞作用中起着核心作用，细胞通过这种内吞作用选择性地内化表面物质。在这里，我们报道了网格蛋白和AP2在凋亡细胞吞噬中的重要作用。在秀丽隐杆线虫中，网格蛋白重链CHC-1和AP2单个组分的耗损导致生殖细胞尸体的大量积累，这是由于细胞尸体吞噬和吞噬体成熟的缺陷导致的。CHC-1和AP2组分以相互依赖的方式与吞噬体相关。重要的是，我们发现吞噬受体CED-1与AP2的α亚基相互作用，而CED-6/Gulp接头与CHC-1和AP2复合物形成复合物，这可能介导了CED-1信号通路触发的细胞尸体吞噬所需的肌动蛋白细胞骨架的重排。此外，CHC-1和AP2通过与LST-4/Snx9/18/33和DYN-1/dynamin形成复合物促进吞噬体结合，从而促进尸体降解所需的吞噬体成熟。这些发现揭示了网格蛋白和AP2的非经典作用，并确立了它们在吞噬受体介导的凋亡细胞清除中不可或缺的调节因子。
Clathrin and the multi-subunit adaptor protein complex AP2 are central players in clathrin-mediated endocytosis by which the cell selectively internalizes surface materials. Here, we report the essential role of clathrin and AP2 in phagocytosis of apoptotic cells. In Caenorhabditis elegans, depletion of the clathrin heavy chain CHC-1 and individual components of AP2 led to a significant accumulation of germ cell corpses, which resulted from defects in both cell corpse engulfment and phagosome maturation required for corpse removal. CHC-1 and AP2 components associate with phagosomes in an inter-dependent manner. Importantly, we found that the phagocytic receptor CED-1 interacts with the α subunit of AP2, while the CED-6/Gulp adaptor forms a complex with both CHC-1 and the AP2 complex, which likely mediates the rearrangement of the actin cytoskeleton required for cell corpse engulfment triggered by the CED-1 signaling pathway. In addition, CHC-1 and AP2 promote the phagosomal association of LST-4/Snx9/18/33 and DYN-1/dynamin by forming a complex with them, thereby facilitating the maturation of phagosomes necessary for corpse degradation. These findings reveal a non-classical role of clathrin and AP2 and establish them as indispensable regulators in phagocytic receptor-mediated apoptotic cell clearance.
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影响因子：
3.7
作者：
Hamon Y;Trompier D;Ma Z;Venegas V;Pophillat M;Mignotte V;Zhou Z;Chimini G
通讯作者：
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影响因子：
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Lu N;Shen Q;Mahoney TR;Liu X;Zhou Z
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Zhou Z
影响因子：
4
作者：
Lundmark, Richard;Carlsson, Sven R.
通讯作者：
Carlsson, Sven R.